Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/115220
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Tubulin-based structure-affinity relationships for antimitotic Vinca alkaloids |
Autor: | Coderch, Claire; Morreale, Antonio; Gago, Federico CSIC ORCID | Palabras clave: | Truncated octahedron Halichondria okadai Colchicine-binding Binding energy analysis Vinblastine Computer simulations Tubulin Molecular dynamics Vinca alkaloids Antimitotic drugs |
Fecha de publicación: | 2012 | Citación: | Anti-Cancer Agents in Medicinal Chemistry 12: 219- 225 (2012) | Resumen: | The Vinca alkaloids are a group of widely used anticancer drugs, originally extracted from the Madagascar periwinkle, that disrupt microtubule dynamics in mammalian cells by interfering with proper assembly of α,β-tubulin heterodimers. They favor curved tubulin assemblies that destabilize microtubules and induce formation of spiral aggregates. Their binding energy profiles have been characterized by means of sedimentation velocity assays and the binding site of vinblastine at the interface between two tubulin dimers (α 1β 1-α 2β 2) has been ascertained by X-ray crystallographic studies on a complex of tubulin with the stathmin-like domain of protein RB3, albeit at relatively low resolution. Here we use molecular modeling and simulation techniques to build, refine and perform a comparative analysis of the three-dimensional complexes of vinblastine, vincristine, vinorelbine and vinflunine with a β 1α 2-tubulin interface in explicit water to rationalize the binding affinity differences in structural and energetic terms. Our results shed some more light into the binding determinants and the structure-activity relationships of these clinically useful agents. | URI: | http://hdl.handle.net/10261/115220 | DOI: | 10.2174/187152012800228841 | Identificadores: | doi: 10.2174/187152012800228841 issn: 1871-5206 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
SCOPUSTM
Citations
40
checked on 07-mar-2024
WEB OF SCIENCETM
Citations
40
checked on 26-feb-2024
Page view(s)
292
checked on 23-abr-2024
Download(s)
112
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.